The University of Wisconsin School of Medicine and Public Health (UWSMPH) is a professional school for the study of medicine and public health at the University of Wisconsin–Madison. It is one of only two medical schools in Wisconsin, along with the Medical College of Wisconsin in Milwaukee, and the only public one. UWSMPH's main building, the Health Sciences Learning Center, is located at the western end of UW–Madison's campus, adjacent to the UW Health University Hospital, its primary affiliated teaching hospital, as well as the Wisconsin Institutes for Medical Research. UWSMPH is active in teaching and research, and extramural research grants received by UWSMPH totaled US$367.8 million in 2017-18, accounting for 40 per cent of all research grants received by UW–Madison.
Proteinuria is a post-kidney transplant complication associated with adverse patient and graft outcomes. While proteinuria guidelines in non-transplant chronic kidney disease have adapted to emerging evidence, similar guidelines in transplantation ought to as well. Recent evidence suggests that quantifiable albuminuria, even in patients without detectable proteinuria significantly impacts kidney transplant recipients, increasing odds of graft failure 25-fold, all-cause mortality nearly 5-fold, cardiovascular mortality nearly 7-fold, and malignancy-related mortality more than 8-fold. Such data along with the contemporary paradigm shift in field-changing anti-proteinuric therapeutics have prompted this examination of post-transplant proteinuria. In this review, we aim to refine current understanding of post-transplant proteinuria as well as highlight key broad strategies beyond rejection applicable to the broader audience of nephrologists involved in the care of kidney transplant recipients.
Background Diffuse Midline Glioma H3K27-altered (DMG) is an extremely aggressive and lethal childhood brain cancer that grows within the midline structure of the brain. Current treatment options are only palliative, making DMG in desperate need for therapeutic breakthroughs. One of the major challenges limiting the study of DMG is the lack of reliable preclinical models. In-vivo mouse models are expensive and technically challenging and in-vitro cell culture models lack the essential components of tumor microenvironment (TME) needed to recapitulate the complex biology of these tumors. Scalable human planar neural organoids (PNOs) with multi-cellular make-up can serve as a cost effective and reliable model system to cap-ture DMG biology and allow effective species matched drug testing in-vitro. Methods Using 3 separate DMG patient derived xenograft (PDX) cell lines, we spatially profiled a novel scalable human iPSC-derived PNO system containing neurons, functional astrocytes and microglia using the NanoString GeoMx spatial transcriptomics system. Results We found that all three cell lines interact with and integrate into the human PNOs, demonstrating favorable growth conditions in a complex co-culture. Across spatially resolved regions of interest (ROI's) tumor cells individually interact with microglia and astrocytes and transcriptomic profiling of these mixed cell ROI's shows differences in the genetic signa-tures of both the normal cells (microglia/astrocytes) and the tumor cells. When compared to biopsies obtained directly from DMG patients, DMG cells within PNOs correlate strongly at both transcriptomic and proteomic levels. The multi-cellular PNOs also enabled drug target bystander toxicity screening not possible in a traditional tumor cell only monoculture. Conclusion This study provides a proof-of-concept for scalable PNO modeling for DMG and underscores the translational relevance of this model system.
Background Diagnosing acute kidney injury (AKI) in preterm neonates remains difficult, and its underlying causes are not well understood. This study aimed to compare urinary metabolite profiles in preterm neonates with and without AKI. Methods We conducted a prospective observational study of neonates born at < 32 weeks' gestation. AKI was staged using the modified neonatal definition. Urine samples were collected every six hours using cotton in diapers. Metabolomic profiling was performed via liquid chromatography mass spectrometry (LC-MS). Data were acquired in polarity switching mode and processed using Compound Discoverer 3.3. Results Among 32 enrolled neonates (median birth weight 1.25 kg, gestational age 29 weeks), five developed AKI. A total of 987 urine samples were collected, with 522 age- and sex-matched samples from 16 individuals included in the final analysis. Principal component (PC) analysis revealed that PC1 and PC2 accounted for 15.82% and 11.61% of sample variance, respectively. Comparison of samples from neonates with and without AKI identified significantly elevated levels of furosemide, acesulfame, kynurenic acid, and hexaethylene glycol in the AKI group (p < 0.05, log2 fold change > 1) and with significant differences between metabolites within biochemical pathways including branch chain fatty acid oxidation, tyrosine metabolism, and carnitine synthesis. Longitudinal analysis also revealed metabolite changes preceding AKI onset, with distinct profiles compared to neonates who did not develop AKI. Conclusions Preterm neonates with AKI exhibit distinct urinary metabolomic profiles compared to those without AKI. These findings suggest potential for metabolomic signatures to aid in early AKI detection, phenotype classification, and identification of therapeutic targets. Further research is needed to refine compound identification and timing of metabolite changes.
Sarcopenia after liver transplantation is poorly characterized in recipients with metabolic dysfunction-associated steatotic liver disease (MASLD) and severe obesity. We evaluated longitudinal changes in psoas muscle index (PMI) after transplantation and examined whether PMI trajectory was associated with post-transplant survival. We performed a retrospective single-center study of adults with MASLD and body mass index ≥ 35 kg/m2 who underwent orthotopic liver transplantation between January 2015 and June 2023. PMI was measured on computed tomography at the L3 level before transplantation and at 6 months, 1 year, 3 years, and 5 years when available. Longitudinal change was assessed using linear mixed-effects models adjusted for survival status. Survival analyses included Kaplan–Meier estimation and univariate logistic regression. Seventy-three recipients were included; mean age was 59.3 years, 50.7
Social Determinants of Health (SDoH) profoundly influence cancer outcomes, yet their distribution among racially diverse gastrointestinal (GI) cancer patients remains understudied. This study examines racial differences in SDoH between non-Hispanic White (NHW) and Non-White (including Asian, African American, and Hispanic) patients with gastrointestinal (GI) cancers using data from the All of Us Research Program. A total of 6,620 participants with GI cancer were identified using ICD-10 and SNOMED codes, of whom 1,831 completed the SDoH survey and were included in the analysis. Descriptive statistics summarized SDoH constructs such as social cohesion, support, and neighborhood disorder. Variables were categorized using validated scoring tools or grouped into tertiles. Group comparisons used chi-square, t-tests, or Wilcoxon rank-sum tests. Among the 1,831 participants included in the overall cohort, 80.7
